Injection of biomolecules, genes and cells is commonly used in biological therapies. For example, intra-discal injection of biomolecules such as transforming growth factor-beta 1 has been used in the treatment of degenerative intervertebral discs (IVD) (Zhao et al.; 2007). In addition, direct transfection of disc cells in vivo, as well as transfection of disc cells in vitro followed by the return of the transfected cells back to the disc, has been used in gene therapy (Freimark et al., 2009).
Recently, mesenchymal stem cell (MSC)-based therapy for treating degenerative discs has received much attention (Freimark et al., 2009). Many animal models have demonstrated the value of mesenchymal stem cell (MSC)-based therapy for treating degenerative discs. Long term survival of MSCs has been demonstrated in a rabbit model (Zhang et al., 2005). Effective arrest of disc degeneration has also been demonstrated in rabbit and canine models (Leung et al., 2006; Vadala et al., 2008). Early phase clinical trials also reported that mesenchymal stem cell (MSC)-based therapy produces encouraging results in alleviating symptoms and improving disc stability (Yoshikawa et al., 2010).
A critical problem common to all intra-discal injection is the leakage or backflow of the injected materials through the injection portal caused by the large intra-discal pressure. Matrix-assisted cell delivery has been proposed; however, only fewer than the 3% of the injected cells were found in the disc after injection (Bertram et al., 2005). Hydrogels made of natural biomaterials such as hyaluronan gel and atellocollagen as well as hydrogels made of synthetic biomaterials such as 2-hydroxyethyl methacrylate have been used in intra-discal injection (Sakai et al. 2003; Sakai et al., 2005; Sykova et al, 2006). However, hydrogels usually have insufficient viscosity and stiffness; this results in an immediate loss of a majority of injected cells (>96%) due to the backflow of the injected materials via the injection path. The problem of leakage or backflow of injected materials is reported in a degenerative IVD model in rat, and is observed by the present inventors using hydrogel or collagen microspheres as injection materials. The current cell-based therapy results in low cell retention inside the disc, a significant cell leakage, the formation of osteophytes, and the lack of adequate amount of MSCs inside the disc (Sobajima et al., 2008; Roberts et al., 2008; Vadala et al., 2011; Sobajima et al., 2004). Moreover, the formation of osteophyte may attribute to cell leakage as the presence of MSCs was demonstrated within the osteophyte tissue (Vadala et al., 2011).
The leakage of injected cells and other biomaterials negatively affects the safety and efficacy of cell-based therapy in disc degeneration. There is a need of developing improved devices for preventing leakage of injected materials in biological therapy.